My laboratory research explores alternative pre-mRNA splicing in prostate cancer (PCa) biology transcriptomic changes during PCa treatment, and liquid biopsy molecular biomarkers of treatment outcomes. My clinical research investigates patterns of treatment outcomes for PCa patients.
The effect of comorbidity on prostate-cancer specific mortality: a prospective observational study. J Clin Oncol (2017) 35(31):3566-3574. PMID: 28930493
Next-generation Sequencing of Advanced Prostate Cancer Treated with Androgen-deprivation Therapy. Eur Urol (2014) 66(1):32-9 PMID: 24054872
The RNA-binding and adaptor protein Sam68 modulates signal-dependent splicing and transcriptional activity of the androgen receptor. J Pathol (2008) 215(1):67-77 PMID: 18273831
Treatment-resistant metastasis is the predominant cause of prostate cancer (PCa)-related death. My laboratory research programme explores how post-transcriptional mechanisms of gene regulation underlie both the metastatic and treatment-resistant PCa phenotypes.
A major focus in our group is the role of a ubiquitous genetic process, termed alternative pre-mRNA splicing, where coding (exons) and non-coding (introns) regions of a gene are shuffled to create structurally/functionally different protein isoforms. Alternative splicing is controlled by trans-acting RNA-binding proteins (RBPs), which bind cis-elements within the nascent pre-mRNA. RBPs also have key roles in other aspects of RNA processing and metabolism.
We are exploring the expression and localization of RBPs in primary tumours and their contribution to the differential regulation of the transcriptome and proteome during disease progression. We are also exploring how RNA-based liquid biopsy biomarkers may improve the prediction of treatment outcomes for PCa patients.
Our clinical research utilises large population-based PCa patient datasets to explore patterns associated with different treatment outcomes.
Ultimately, we hope to identify clinical risk prediction models and biomarkers, as well as delineate novel therapeutic strategies for metastatic and treatment-resistant PCa.
Reply by Authors Xu L, Mao X, Grey A et al. The Journal of urology (2020) 203(7) 81-82
Identification of altered biological processes in heterogeneous RNA-sequencing data by discretization of expression profiles. Lauria A, Peirone S, Giudice MD et al. Nucleic Acids Res (2019) (2)
Noninvasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells. Xu L, Mao X, Grey A et al. The Journal of Urology 203(1) 101097JU000000000000-101097JU000000000000
Pathological Findings and Magnetic Resonance Imaging Concordance at Salvage Radical Prostatectomy for Local Recurrence following Partial Ablation Using High Intensity Focused Ultrasound. Thompson JE, Sridhar AN, Tan WS et al. J Urol (2019) 201(1) 1134-1143
Androgen Receptor Burden and Poor Response to Abiraterone or Enzalutamide in TP53 Wild-Type Metastatic Castration-Resistant Prostate Cancer. De Laere B, Rajan P, Grönberg H et al. JAMA Oncol (2019) (1)
PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens Heavey S, Costa H, Pye H et al. Prostate (2019) 79(7) 768-777
TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer De Laere B, Oeyen S, Mayrhofer M et al. Clinical Cancer Research (2019) 25(7) 1766-1773
Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis Mayrhofer M, De Laere B, Whitington T et al. Genome Medicine (2018) 10(7)
Androgen-dependent alternative mRNA isoform expression in prostate cancer cells. Munkley J, Maia TM, Ibarluzea N et al. F1000Research (2018) 7(1) 1189-1189
A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia. Foxler DE, Bridge KS, Foster JG et al. EMBO Mol Med (2018) (1)